STAT3

 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the STAT3 gene.[5] It is a member of the STAT protein family.

STAT3
Stat3 structure.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSTAT3, ADMIO, APRF, HIES, signal transducer and activator of transcription 3, ADMIO1
External IDsOMIM: 102582 MGI: 103038 HomoloGene: 7960 GeneCards: STAT3
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for STAT3
Genomic location for STAT3
Band17q21.2Start42,313,324 bp[1]
End42,388,568 bp[1]
RNA expression pattern
PBB GE STAT3 208992 s at fs.png

PBB GE STAT3 gnf1h01250 at fs.png

PBB GE STAT3 208991 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6774

20848

Ensembl

ENSG00000168610

ENSMUSG00000004040

UniProt

P40763

P42227

RefSeq (mRNA)

NM_011486
NM_213659
NM_213660

RefSeq (protein)

NP_035616
NP_998824
NP_998825

Location (UCSC)Chr 17: 42.31 – 42.39 MbChr 11: 100.89 – 100.94 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

FunctionEdit

STAT3 is a member of the STAT protein family. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), form homo- or heterodimers, and translocate to the cell nucleus where they act as transcription activators. Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons, epidermal growth factor (EGF), Interleukin (IL-)5 and IL-6. Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by Mitogen-activated protein kinases (MAPK)[6] and through c-src non-receptor tyrosine kinase.[7][8] STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis.[9]

STAT3-deficient mouse embryos cannot develop beyond embryonic day 7, when gastrulation begins.[10] It appears that at these early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs). Indeed, LIF, which is supplied to murine ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means.[11]

STAT3 is essential for the differentiation of the TH17 helper T cells, which have been implicated in a variety of autoimmune diseases.[12] During viral infection, mice lacking STAT3 in T-cells display impairment in the ability to generate T-follicular helper (Tfh) cells and fail to maintain antibody based immunity.[13]

Clinical significanceEdit

Loss-of-function mutations in the STAT3 gene result in Hyperimmunoglobulin E syndrome, associated with recurrent infections as well as disordered bone and tooth development.[14]

Gain-of-function mutations in the STAT3 gene have been reported to cause multi-organ early onset auto-immune diseases; such as thyroid disease, diabetes, intestinal inflammation, and low blood counts,[15] while constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis.[16][17][18][19] It has anti-apoptotic as well as proliferative effects.[16]

STAT3 can promote oncogenesis by being constitutively active through various pathways as mentioned elsewhere. A tumor suppressor role of STAT3 has also been reported.[20][21][22] In the report on human glioblastoma tumor, or brain cancer, STAT3 was shown to have an oncogenic or a tumor suppressor role depending upon the mutational background of the tumor. A direct connection between the PTEN-Akt-FOXO axis (suppressive) and the leukemia inhibitory factor receptor beta (LIFRbeta)-STAT3 signaling pathway (oncogenic) was shown.

Increased activity of STAT3 in cancer cells, leads to changes in the function of protein complexes that control expression of inflammatory genes, with result profound change in the secretome and the cell phenotypes, their activity in the tumor, and their capacity for metastasis.[23]

InteractionsEdit

STAT3 has been shown to interact with:

  • AR,[24][25]
  • ELP2,[26]
  • EP300,[27]
  • EGFR,[28][29]
  • HIF1A,[30]
  • JAK1,[24][31]
  • JUN[32]
  • KHDRBS1,[33]
  • mTOR,[34][35]
  • MYOD1,[36]
  • NDUFA13,[37]
  • NFKB1,[38]
  • NR3C1,[39][40]
  • NCOA1,[41]
  • PML,[42]
  • RAC1,[43]
  • RELA,[38]
  • RET,[28][44][45]
  • RPA2,[46]
  • STAT1,[31][47][48]
  • Stathmin,[49]
  • Src,[50] and
  • TRIP10.[51]
  • KPNA4.[52]

Niclosamide seems to inhibit the STAT3 signalling pathway.[53]

This article uses material from the Wikipedia article
 Metasyntactic variable, which is released under the 
Creative Commons
Attribution-ShareAlike 3.0 Unported License.